This application proposes neurophysiological and anatomical studies to reveal the mechanisms by which alterations in the pattern of afferent neuronal activity during development may lead to changes in neural connections in the cat's visual cortex. Oculardominance columns in layer IV of the cat's visual cortex form during postnatal life by a progressive segregation of the geniculocortical afferents serving the two eyes. We have found that pharmacological blockade of spike activity transmitted from the retina to the brain during this period of segregation prevents or delays the formation of these columns. We will exploit this phenomenon by introducing defined patterns of activity into the two optic nerves using electrical stimulation in order to test hypotheses about the role of afferent spike activity in the formation of these columns. A mechanism by which changes in the activity of postsynaptic cells might influence their presynaptic inputs is modification of the local ionic microenvironment; using ion-sensitive microelectrodes in combination with conventional recordings, measurements will be made in both young and adult cats of activity-dependent changes in extracellular calcium and potassium. Experiments combining microelectrode recording with deoxyglucose measurements on the same piece of cortical tissue will reveal the relationship between neuronal spike activity in the cat's visual cortex and local cerebral glucose utilization, as measured using the 14C-2-deoxyglucose (2DG) technique. We will discover the extent to which this relationship depends on the cortical layer, the age of the animal, or the region or cortex studied. These techniques will be used to investigate the adult form and normal development of orientation columns in the cat's visual cortex. Effects of abnormal early visual experience will be investigated in kittens deprived of pattern vision or reared with vision of only a restricted range of orientations. Findings of these studies should answer a fundamental question of developmental neurobiology--how changes in activity can result in permanent changes in neural connections. The findings will also be significant for our conception of the structure and physiology of the visual cortex, and for the ophthalmological treatment of amblyopia.